Standing
Undergraduate
Type of Proposal
Oral Research Presentation
Faculty
Faculty of Science
Faculty Sponsor
Dr. Lisa Porter
Proposal
Multiple myeloma (MM) is an aggressive hematopoietic malignancy with a poor prognosis that is caused by the abnormal growth of plasma cells in the bone marrow. Cyclin-dependent kinase inhibitors (CKIs) have been explored as a possible treatment for MM, with limited clinical success. We postulate that the cyclin-like protein, Spy1 (SPDYA), which is capable of overriding cell-cycle checkpoints, may play a role in limiting therapeutic effectiveness. To support this hypothesis, we have found that Spy1 is highly expressed in MM patient samples and human cell lines. We aim to explore the role that Spy1 plays in CKI resistance in MM using a variety of in vitro and in vivo techniques. Firstly, we intend to create and optimize an in vitro platform to study MM using patient samples collected from clinicians at Windsor Regional Hospital. Using this culture, and human cell lines, we intend to investigate the methylation status of Spy1 and other MM genes in Spy1 overexpression and knockout conditions to see the effects of epigenetic regulation. Then, we will perform drug and toxicity assays with standard CKIs using our Spy1 overexpression and knock-down lines to observe response to CKIs, expecting lines with higher Spy1 to demonstrate increased therapy resistance. Finally, our cells with manipulated Spy1 levels will be injected into zebrafish to test the effects of CKIs in vivo. Collectively, we aim to explore the role Spy1 may play in resistance to CKI therapy in MM, to improve disease understanding and identify areas treatments may be improved.
Availability
March 29-April 1st
Spy1 Levels Predict Sensitivity of Refractory Multiple Myeloma to Therapy
Multiple myeloma (MM) is an aggressive hematopoietic malignancy with a poor prognosis that is caused by the abnormal growth of plasma cells in the bone marrow. Cyclin-dependent kinase inhibitors (CKIs) have been explored as a possible treatment for MM, with limited clinical success. We postulate that the cyclin-like protein, Spy1 (SPDYA), which is capable of overriding cell-cycle checkpoints, may play a role in limiting therapeutic effectiveness. To support this hypothesis, we have found that Spy1 is highly expressed in MM patient samples and human cell lines. We aim to explore the role that Spy1 plays in CKI resistance in MM using a variety of in vitro and in vivo techniques. Firstly, we intend to create and optimize an in vitro platform to study MM using patient samples collected from clinicians at Windsor Regional Hospital. Using this culture, and human cell lines, we intend to investigate the methylation status of Spy1 and other MM genes in Spy1 overexpression and knockout conditions to see the effects of epigenetic regulation. Then, we will perform drug and toxicity assays with standard CKIs using our Spy1 overexpression and knock-down lines to observe response to CKIs, expecting lines with higher Spy1 to demonstrate increased therapy resistance. Finally, our cells with manipulated Spy1 levels will be injected into zebrafish to test the effects of CKIs in vivo. Collectively, we aim to explore the role Spy1 may play in resistance to CKI therapy in MM, to improve disease understanding and identify areas treatments may be improved.